What medicine-exposed rats reveal about the next urban zoonotic threat

A new study reveals that urban rats are absorbing human medicines from polluted environments, and these hidden pharmaceutical exposures may be linked to changes in the pathogens they carry.

Pharmaceutical Pollutants in Urban Rats Are Linked to Zoonotic Infection Risk. Image Credit: torook / Shutterstock

In a recent study published in the journal Environmental Science and Technology Letters, researchers investigated the presence of active pharmaceutical ingredients (APIs) in urban rats and their associations with zoonotic infections.

Pharmaceutical Pollutants and Zoonotic Risk 

Pharmaceutical residues are widespread in the environment and may pose health risks to humans and wildlife. APIs are often incompletely metabolized before excretion and may not be eliminated during wastewater treatment. While API levels in the environment are lower than therapeutic doses, chronic, low-level exposure may subtly affect behavior, physiology, and microbiome, with meaningful ecological ramifications.

APIs can affect wildlife infection dynamics by altering behavior and immunity. For instance, disruptions in social hierarchies in brown trout have been observed upon exposure to an anxiolytic, oxazepam, altering their stress dynamics and aggressive interactions. Moreover, chronic exposure to antibiotics in the environment could drive antimicrobial resistance in the host microbiome, favoring resistant strains.

Most human pathogens, ~60%, have zoonotic origins, which disproportionately impact low-income communities. Poor sanitation, increased access to pharmaceuticals, and high human density raise concerns about environmental pollution from APIs. Given the projections that low-income urban regions will have the most population growth by 2050, understanding how environmental APIs shape disease dynamics in zoonotic reservoirs is crucial.

Potential mechanisms of infection regulation in wild rats exposed to pharmaceuticals. Urban rats, which are closely associated with human activities including waste and sewerage, can uptake various Active Pharmaceutical Ingredients (APIs) from their environment. Once transported into the rats’ tissues, we hypothesize that these compounds trigger a range pharmaceutical effects with potential consequences for the rats’ infection risk. For zoonotic pathogens, this can also influence human disease risks.

Potential mechanisms of infection regulation in wild rats exposed to pharmaceuticals. Urban rats, which are closely associated with human activities including waste and sewerage, can uptake various Active Pharmaceutical Ingredients (APIs) from their environment. Once transported into the rats’ tissues, we hypothesize that these compounds trigger a range pharmaceutical effects with potential consequences for the rats’ infection risk. For zoonotic pathogens, this can also influence human disease risks.

Urban Rat API Exposure 

In the present study, researchers assessed the presence of APIs in urban rats (Rattus rattus and Rattus norvegicus) from low-income urban communities and their associations with zoonotic infections. Urban rats were collected from seven slums in Salvador, Brazil. Rats were euthanized, and brain tissue was harvested for testing the presence of 97 APIs using liquid chromatography-tandem mass spectrometry.

The API panel comprised diverse drug classes, including antibiotics, antipsychotics, and antidepressants, detected in wastewater. The limits of quantification were determined for each analyte. The researchers investigated whether API detection was associated with infection by locally prevalent pathogens, Leptospira spp., Toxoplasma gondii, Angiostrongylus spp., Capillaria spp., and Seoul orthohantavirus (SEOV).

Leptospira bacteria were detected using kidney immunofluorescence imprints and quantitative real-time polymerase chain reaction. A modified Hoffman sedimentation technique was used to determine infections by Capillaria and Angiostrongylus helminths. Further, T. gondii, a protozoan parasite, was detected using a nested polymerase chain reaction.

An enzyme-linked immunosorbent assay was used to detect SEOV. Chi-squared tests examined co-occurrence among the six most frequently detected APIs. Associations between API detection and infection status were assessed using binomial generalized linear models (GLMs). Finally, environmental predictors of API detection were explored using a similar GLM approach. Because the study was observational and cross-sectional, the models could identify associations but could not establish causality or define the underlying mechanisms.

Urban Rat Pharmaceutical Detection 

The researchers screened brain tissues from 152 urban rats, including 127 R. norvegicus, four R. rattus, and 21 of unknown species. In total, 18 APIs were detected in 55% of rats. Detected APIs spanned various drug classes, including antihistamines, antibiotics, stimulants, antidepressants, and antipsychotics.

Among rats with detectable APIs, nearly 30% contained multi-compound mixtures. Citalopram was the most frequently detected API, present in 26% of rats, followed by donepezil (14%), azithromycin (9%), caffeine (6%), clindamycin (6%), and haloperidol (5%). There were distinct association patterns between infection status and API detection, varying by pathogen.

Rats with any detectable API had a 74% lower probability of Leptospira infection, whereas those with azithromycin had a 91% lower probability. Notably, the probability of Capillaria infection was threefold higher in rats with detectable citalopram than in other rats. Moreover, rats with detectable citalopram were more than twice as likely to have SEOV infection as others, although this association was near-significant.

The risk of Angiostrongylus infection was also suggested to be several-fold higher in rats containing clindamycin, but this near-significant estimate was imprecise and based on a small sample. Notably, older rats had a higher probability of Leptospira infection, while female rats had an increased probability of Capillaria infection. The six most commonly detected compounds had distinct environmental predictors, suggesting heterogeneity in the sources/routes of API absorption across compounds.

Environmental API Infection Implications

Taken together, more than half of the tested urban rats contained APIs in their brains, with nearly 30% of API-positive rats containing multi-compound mixtures. The study identified associations between API detection in rats and the probability of infection with locally prevalent pathogens. Rats with detectable azithromycin were 91% less likely to be infected with Leptospira, a zoonotic pathogen that causes one million cases of leptospirosis in humans each year.

Notably, rats with any detectable API other than azithromycin were also less likely to have Leptospira infection, suggesting broader effects of pharmaceuticals. However, the authors note that some key associations were marginal after false discovery rate correction and should be interpreted as hypothesis-generating rather than definitive evidence of pharmaceutical effects. Overall, the findings provide evidence linking environmental pharmaceutical pollutants to increased infection risk in wildlife. Further research is needed to explore the mechanisms through which APIs modulate infection risk, investigate long-term consequences, and develop risk mitigation strategies.

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Journal reference:
  • Sundberg AJ, Cerveny D, Costa F, et al. (2026). Pharmaceutical Pollutants in Urban Rats Are Linked to Zoonotic Infection Risk. Environmental Science & Technology Letters, 13(5), 656-663. DOI: 10.1021/acs.estlett.5c00867, https://pubs.acs.org/doi/10.1021/acs.estlett.5c00867
Tarun Sai Lomte

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Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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